HFIP Promoted C3 Alkylation of Lawsone and 4-Hydroxycoumarin with Alcohols by Dehydrative Cross-Coupling

Article abstract of DOI:10.1021/acs.joc.0c01207

An environmentally benign system for the direct alkylation of lawsones and 4-hydroxycoumarins with alcohols in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) is reported. The reaction proceeded smoothly via a dehydrative cross-coupling process by utilizing the unique properties of HFIP. A variety of alkylated products and subsequent one-pot cyclized products (pyranonaphthoquinones and pyranocoumarins) could be obtained in 40-93% yields.

Full text of DOI:10.1021/acs.joc.0c01207

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Article
HFIP Promoted C3-Alkylation of Lawsone and 4-
Hydroxycoumarin with Alcohols by Dehydrative Cross-Coupling
Yixin Chen, Yurong Wang, Rong Zhong, and Jinshan Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01207 • Publication Date (Web): 28 Jul 2020
Downloaded from pubs.acs.org on July 29, 2020
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HFIP Promoted C3-Alkylation of Lawsone and 4-Hydroxycoumarin
with Alcohols by Dehydrative Cross-Coupling
Yixin Chen,a Yurong Wang,a Rong Zhong,a Jinshan Li*b
aSchool of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, P.
R. China.
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bAdvanced Research Institute and Department of Chemistry, Taizhou University, 1139 Shifu
Avenue, Taizhou 318000, P. R. China.
E-mail: lijinshan@tzc.edu.cn
Graphical Abstract
ABSTRACT
An environmentally benign system for the direct alkylation of lawsones and 4-hydroxycoumarins
with alcohols in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) is reported. The reaction proceeded
smoothly via a dehydrative cross-coupling process by utilizing the unique properties of HFIP. A
variety of alkylated products and subsequent one-pot cyclized products (pyranonaphthoquinones
and pyranocoumarins) could be obtained in 40‒93% yields.
INTRODUCTION
C3-Alkylated lawsones are valuable structural motifs which have wide range application in natural
products and pharmaceutical industry due to their unique biological properties such as
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antibacterial, antifungal, anticancer, antiviral, and antiprotozoal activities.1 Examples include
lapachol, dunniol, atovaquone, buparvaquone, streptocarpone, α-lapachone and α-dunnione
(Figure 1).2 These comprehensive bioactivity profiles and drug-like characteristics have attracted
extensive attention from pharmacologists and synthetic organic chemists. As a consequence, great
efforts have been made to develop various methods for regioselective synthesis of C3-alkylated
lawsones in the past decades.3 Among existing methods for synthesizing C3-substituted lawsone
derivatives, the C–C bond forming reactions between lawsone and different alkylating agents
would represent one of the most straightforward synthetic methods. The traditional alkylation of
lawsone with alkyl halides in the presence of a stoichiometric amount of base usually gives a
mixture of C- and O-alkylated products with low yields and regioselectivities (Scheme 1 A).4
Silver-mediated alkylation of lawsone using carboxylic acids or peroxides provides an alternative,
but harsh reaction conditions limit its scope (Scheme 1 B).5 Recently, Cheng and co-workers
reported a DDQ-promoted cross-dehydrogenative coupling reaction between lawsone and
1,3-diarylpropene for the synthesis of C3-alkylated lawsone (Scheme 1 C).6 However, the use of a
stoichiometric amount of DDQ often generates large quantities of hydroquinone as by-product,
which makes purification process difficult.
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Figure 1. Representative biologically active natural molecules and drugs containing C3-alkylated
lawsone moieties.
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Scheme 1. Different C3-Alkylation Strategies of Lawsones.
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Taking hazardous waste minimization and environmental sustainability into account, the
metal-free direct substitution of alcohols via dehydrative cross-coupling is highly desired and
represents a much ecologically benign, step- and atom-economical approach with water as the
only by-product.7 However, the reactions using the corresponding alcohols have not been well
studied. Only in rare cases, palladium catalyst and high temperature environment were demanded
to promote the benzylation and allylation of lawsone with specific alcohol or its acetate, which
was probably due to the high activation barrier for C–OH scission (85−91 kcal mol−1).8 In this
regard, a catalyst-free and milder methodology for the C3-alkylation of lawsone is worthy to
explore. Fluorinated alcohols may be considered as a promising alternative to address this
synthetic challenge due to their unique properties such as high polarity, high H-bond donor ability,
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high dielectric constant and low nucleophilicity for cation stabilization.9 The above properties of
fluorinated alcohols would provide the possibility of performing this dehydrative cross-coupling
reaction using alcohols in a user-friendly and environmentally friendly transformation (Scheme 1
D).
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RESULTS AND DISCUSSION
The alkylation of lawsone 1a with 1,3-diarylpropenol (chalcol) 2a was selected as the model
reaction for the reaction condition optimization. We first examined the reaction in pure
2,2,2-trifluoroethanol (TFE) solvent, and the reaction mixture was stirred at room temperature
under air. To our delight, C3-alkylated lawsone 3a was obtained in 68% yield with excellent
regioselectivity (Table 1, entry 1). Another fluorinated solvent with a much stronger polarity,
ionizing
power,
Brønsted
acidity,
and
hydrogen-bonding
ability,
1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), was then tested. Unexpectedly, the transformation
proceeded rapidly to afford the desired product in 87% yield in 10 minutes (entry 2). Other
nonfluorinated alcohols, such as isopropanol and ethanol, as well as water with high polarity and
hydrogen bonding capability were selected as the solvents, none of the desired product was
obtained with the formation of unwanted etherified or dimerizated product of chalcol 2a (entries
3‒5). No product was detected when perfluorohexane was used as solvent, which indicating that
fluorine atom is not the sole factor promoting the reaction smoothly (entry 6). The employment of
weak acidic media to produce C3-alkylated lawsone was unsuccessful (entry 7). When HFIP was
used as a mixed solvent, the yields of the expected product decreased greatly (entries 8‒11).
Regulating the reaction temperature did not result in any further improvement in yields. Thus, the
optimal condition is that the reaction was stirred in HFIP at room temperature without any extra
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catalyst.
Table 1 Optimization of the Reaction Conditions for the C3-Alkylation of Lawsone with Chalcola
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entry
1
solvent
TFEc
Time (h)
1
yield (%)b
68
HFIPd
iPrOH
EtOH
H2O
10 min
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87
trace
0
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0
e
6
C6F14
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CHCl3
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0
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HFIP/ CHCl3 = 1:1
HFIP/ iPrOH = 1:1
HFIP/ EtOH = 1:1
HFIP/ H2O = 1:1
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aReaction conditions: 1a (1.2 mmol), 2a (1.0 mmol) in solvent (5.0 mL) at room temperature unless otherwise
noted. bIsolated yields. cTFE = 2,2,2-trifluoroethanol. dHFIP = 1,1,1,3,3,3-hexafluoro-2-propanol. eC6F14
perfluorohexane.
=
With the optimized reaction conditions established for this dehydrative cross-coupling reaction,
we embarked on the investigation of substrate scope to probe the generality of the reaction. A
series of alcohols 2 were treated with lawsone 1 to form the alkylated products in HFIP at ambient
temperature (Scheme 2). Chalcols bearing electron-donating or electron-withdrawing groups on
the aromatic ring all functioned well in the C3-alkylation of lawsone, affording the desired
product in 61‒87% yields (3a-3e). It should be pointed out that both isomers were detected when
the asymmetrical chalcol 2e was employed, giving the corresponding inseparable products (3e/3e’
= 2:3) in 63% yield. According to forecasting results, it indicates that allyl cations was formed and
rearranged occurred between α- and γ-positions during the reaction. In order to evaluate the scope
and limitations of this methodology, a range of benzyl alcohols were converted under the optimal
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reaction conditions developed for the alkylation of lawsone. Primary, secondary and even
sterically-hindered tertiary benzylic alcohols could react smoothly with lawsone to furnish the
corresponding alkylated products in 66‒82% yields (3f-3k).
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Scheme 2. Dehydrative Cross-Coupling of Lawsones with Alcohols in HFIP.a,b
aReaction conditions: 1 (1.2 mmol), 2 (1.0 mmol) in HFIP (5.0 mL) at room temperature. bIsolated yields based on
2.
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C3-Alkylated coumarins are one of the most important classes of heterocyclic compounds and
known to exhibit a wide spectrum of pharmacological properties including antibiotic, antifungal,
anticoagulant activities.10 A great number of methods have been developed for the C3-alkylation
of 4-hydroxycoumarins by using alcohols with Lewis acids, such as TMSOTf, BF3·Et2O,
Amberlyst IR-120, Bi(OTf)3, Yb(OTf)3, I2, Pd-Sn bimetallic system or microwave.11 However,
high toxicity, corrosion, catalyst waste problems are almost inevitable in these reported processes.
To provide a greener and more efficient method for the alkylation of 4-hydroxycoumarin through
dehydrative cross-coupling strategy, the reaction of 4-hydroxycoumarin 4 and alcohols 2 promoted
by HFIP was studied. Various desired dehydrative coupling products were obtained in 57‒93%
yields under the previous optimized reaction conditions (Scheme 3, 5a-5o).
4-Hydroxy-2-quinolinone 2p was also a viable substrate for the reaction. The corresponding
product 5p was obtained in 40% yield. More interestingly when the hydroxyl group on the
4-hydroxycoumarin was replaced by an amino group, product 5q was obtained in 90% yield. In
addition, it was further found that 3-alkylated 4-hydroxycoumarins related natural products or
drugs, such as Phenprocoumon 5r and Coumatetarlyl 5s could be obtained on a 5.0 mmol scale
from lawsone and 4-hydroxycoumarin upon reaction with corresponding alcohols. Moreover,
Stiripentol, used as an anticonvulsant drug in the treatment of pediatric epilepsy, can be easily
functionalized with 4-hydroxycoumarin by using our newly developed methodology on a gram
scale.
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To demonstrate the synthetic utility of this protocol, we conducted further manipulation by
utilizing the sequential dehydrative cross-coupling/cyclization reactions with lawsone for the
synthesis of pyranonaphthoquinones in a one-pot manner (Scheme 4). This consecutive
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transformation displays the synthetic potential of the developed procedure. The cyclized product
6a was smoothly obtained in 78% yield with the addition of one equivalent of DDQ into the
reaction mixture after the alkylation reaction of lawsone 1a with chalcol 2a finished. Various
pyranonaphthoquinones and pyranocoumarins were provided in 49‒80% yields.
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Scheme 3. Dehydrative Cross-Coupling of 4-Hydroxycoumarins with Alcohols in HFIP.a,b
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aReaction conditions: 4 (1.2 mmol), 2 (1.0 mmol) in HFIP (5.0 mL) at room temperature. bIsolated yields based on
2.
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Scheme 4. One-Pot Sequential Dehydrative Cross-Coupling and Cyclization Reaction for the
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Syntheses of Pyranonaphthoquinones and Pyranocoumarins.
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Scheme 5. Plausible mechanism.
On the basis of results of dehydrative cross-coupling of lawsone with chiral alcohol (Scheme 5a,
98% ee) and previous studies16, a SN1 mechanism was proposed in Scheme 5b. The alcohol is
protonated by HFIP to give an oxonium ion via hydrogen bonding interaction. Then oxonium ion
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is dehydrated to form a stabilized carbocation intermediate, which is attacked by the nucleophilic
reagent lawsone or 4-hydroxycoumarin to give the coupling products.
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CONCLUSIONS
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In summary, a HFIP-promoted dehydrative cross-coupling reaction between lawsones,
4-hydroxycoumarin and alcohols has been developed. The use of alcohols as alkylating agents
avoided the need for pre-activation treatment and water was the sole byproduct utilizing this
method, which would be a more environmentally benign way than existing protocols. In addition,
a series of C3-alkylated lawsone and 4-hydroxycoumarin derivatives with potential bioactivities
could be easily synthesized with the developed approach.
EXPERIMENTAL SECTION
1
General Information. H, 13C and 19F were recorded on Bruker AV 400 MHz instrument at 400
MHz (1H NMR), 100 MHz (13C NMR), as well as 376 MHz (19F NMR). Chemical shifts were
reported in ppm down field from internal Me4Si and external CCl3F, respectively. CDCl3 (7.26
1
1
ppm for H NMR, 77.0 ppm for 13C NMR), or DMSO-d6 (2.50 ppm for H NMR, 39.5 ppm for
1
13C NMR) was used as a reference. Data for H were reported as follows: chemical shift (ppm),
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, m =
multiplet, br = broad singlet), coupling constants (Hz), and integration. Data for 13C NMR were
reported as ppm. High-resolution mass spectra analyses were performed on a Waters SYNAPT
G2-Si Q-TOF mass spectrometer. Melting points were determined using a X-4 digital micro
melting point apparatus. Thin-layer chromatography (TLC) was performed, and visualization of
the compounds was accomplished with UV light (254 nm). Flash column chromatography was
performed on silica gel (200−300 mesh). Chalcols 2a−2e and alcohol 2l were prepared according
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to literature procedures.12 Purchased reagents and solvents were used without further purification.
General Procedure for Preparation of 3-Alkylated Lawsones 3. A mixture of the substrate 1
(1.2 mmol), substrate 2 (1.0 mmol), in HFIP (5.0 mL) was stirred at room temperature for 10 min.
Upon completion of the reaction, the resulting mixture was and concentrated in vacuo. The residue
was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 8:1) to give
the pure product 3; the method is also suitable for the alkylation of 4-hydroxycoumarins 4.
(E)-2-(1,3-Diphenylallyl)-3-hydroxynaphthalene-1,4-dione (3a): orange oil (318 mg, 87% yield,
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1
hexane/EtOAc = 8/1 as the eluent). H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 7.7 Hz, 1H), 8.13
(d, J = 7.6 Hz, 1H), 7.81 (t, J = 7.5 Hz, 1H), 7.73 (t, J = 7.5 Hz, 1H), 7.47 (d, J = 7.6 Hz, 4H),
7.35 (t, J = 7.5 Hz, 4H), 7.30 (s, 1H), 7.26 (t, J = 7.2 Hz, 2H), 7.06 (dd, J = 15.8, 8.9 Hz, 1H), 6.67
(d, J = 15.8 Hz, 1H), 5.44 (d, J = 8.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 183.8, 181.9,
152.8, 141.7, 137.3, 135.2, 133.1, 132.9, 132.5, 129.3, 128.6, 128.6, 128.4, 127.8, 127.5, 127.2,
126.5, 126.5, 126.2, 124.8, 44.1; HRMS (ESI) m/z: [M + Na]+ Calcd for C25H18O3Na 389.1154;
Found 389.1153. Physical and spectral properties of this material were identical to those
previously reported in literature.6
(E)-2-(1,3-Di-p-tolylallyl)-3-hydroxynaphthalene-1,4-dione (3b): orange oil (240 mg, 61%
yield, hexane/EtOAc = 8/1 as the eluent). 1H NMR (400 MHz, CDCl3) δ 7.99 (dd, J = 24.1, 7.3 Hz,
2H), 7.64 (td, J = 7.6, 1.3 Hz, 1H), 7.56 (td, J = 7.5, 1.2 Hz, 1H), 7.47 (s, 1H), 7.22 (d, J = 7.8 Hz,
4H), 7.01 (d, J = 7.5 Hz, 4H), 6.85 (dd, J = 15.3, 9.3 Hz, 1H), 6.48 (d, J = 15.8 Hz, 1H), 5.25 (d, J
= 8.9 Hz, 1H), 2.21 (d, J = 5.4 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 181.9, 152.7, 138.8,
137.2, 136.0, 135.13, 134.5, 133.0, 132.9, 132.2, 129.1, 127.7, 127.1, 126.3, 126.1, 125.1, 43.7,
21.2, 21.1; HRMS (ESI) m/z: [M + Na]+ Calcd for C27H22O3Na 417.1467; Found 417.1469.
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(E)-2-(1,3-Bis(4-chlorophenyl)allyl)-3-hydroxynaphthalene-1,4-dione (3c): orange oil (351 mg,
81% yield, hexane/EtOAc = 7/1 as the eluent). 1H NMR (400 MHz, CDCl3) δ 8.10 (dd, J = 12.7,
8.1 Hz, 2H), 7.78 (t, J = 7.6 Hz, 1H), 7.70 (t, J = 7.5 Hz, 1H), 7.41 (dd, J = 8.5, 3.9 Hz, 4H), 7.27
(d, J = 7.1 Hz, 5H), 6.92 (dd, J = 15.8, 8.8 Hz, 1H), 6.53 (d, J = 15.8 Hz, 1H), 5.30 (d, J = 8.8 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 183.7, 181.6, 152.9, 140.5, 136.0, 135.3, 133.2, 132.7,
131.7, 131.5, 129.6, 129.2, 128.8, 128.0, 127.2, 126.3, 124.0, 121.4, 120.5, 43.6; HRMS (ESI) m/z:
[M + Na]+ Calcd for C25H16Cl2O3Na 457.0374; Found 457.0371.
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(E)-2-(1,3-Bis(4-bromophenyl)allyl)-3-hydroxynaphthalene-1,4-dione (3d): orange oil (402 mg,
77% yield, hexane/EtOAc = 7/1 as the eluent). 1H NMR (400 MHz, CDCl3) δ 8.10 (dd, J = 13.4,
7.6 Hz, 2H), 7.77 (t, J = 7.5 Hz, 1H), 7.69 (t, J = 7.5 Hz, 1H), 7.57 (s, 1H), 7.41 (dd, J = 8.5, 2.7
Hz, 4H), 7.28 (d, J = 3.0 Hz, 2H), 6.92 (dd, J = 15.8, 8.8 Hz, 1H), 6.53 (d, J = 15.8 Hz, 1H), 5.29
(d, J = 8.8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 183.7, 181.6, 152.9, 140.5, 136.0, 135.3,
132.7, 131.7, 131.5, 129.6, 129.2, 128.9, 128.0, 127.2, 126.3, 121.4, 120.5; HRMS (ESI) m/z: [M
+ Na]+ Calcd for C25H16Br2O3Na 546.9343; Found 546.9348.
Mixture of (E)-2-(1-(4-Bromophenyl)-3-phenylallyl)-3-hydroxynaphthalene-1,4-dione and
(E)-2-(3-(4-Bromophenyl)-1-phenylallyl)-3-hydroxynaphthalene-1,4-dione (2:3) (3e and 3e’):
orange oil (280 mg, 63% yield, hexane/EtOAc = 7/1 as the eluent). 1H NMR (400 MHz, CDCl3) δ
8.10 (dd, J = 16.7, 7.6 Hz, 2H), 7.72 (dt, J = 31.9, 7.6 Hz, 2H), 7.54 (s, 1H), 7.41 (dd, J = 8.6, 2.2
Hz, 4H), 7.33 – 7.25 (m, 5H), 7.22 (d, J = 7.1 Hz, 1H), 7.06 – 6.86 (m, 1H), 6.57 (dd, J = 27.3,
15.7 Hz, 1H), 5.34 (dd, J = 19.4, 8.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 181.8, 152.8,
141.4, 136.2, 135.2, 133.1, 132.9, 131.6, 131.4, 131.2, 129.6, 128.6, 128.5, 128.0, 127.8, 127.2,
126.6, 126.2, 44.1; HRMS (ESI) m/z: [M + Na]+ Calcd for C25H17BrO3Na 467.0259; Found
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467.0265. Physical and spectral properties of this material were identical to those previously
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2-Benzhydryl-3-hydroxynaphthalene-1,4-dione (3f): orange oil (258 mg, 76% yield,
hexane/EtOAc = 8/1 as the eluent). 1H NMR (400 MHz, CDCl3) δ 8.11 (dd, J = 20.0, 7.7 Hz, 2H),
7.76 (td, J = 7.6, 1.4 Hz, 1H), 7.68 (td, J = 7.5, 1.3 Hz, 1H), 7.51 (s, 1H), 7.35 – 7.20 (m, 10H),
6.00 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 183.9, 181.8, 153.4, 143.8, 141.1, 135.2, 133.0,
132.8, 128.4, 128.2, 127.5, 127.2, 126.5, 126.4, 126.1, 124.9, 45.9; HRMS (ESI) m/z: [M + Na]+
Calcd for C23H16O3Na 363.0997; Found 363.1003.
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2-Hydroxy-3-tritylnaphthalene-1,4-dione (3g): orange oil (274 mg, 66% yield, hexane/EtOAc =
8/1 as the eluent). 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 7.5 Hz, 1H), 7.99 (d, J = 8.3 Hz, 1H),
7.89 (s, 1H), 7.77 – 7.63 (m, 2H), 7.46 (d, J = 8.6 Hz, 6H), 7.21 (t, J = 7.7 Hz, 6H), 7.11 (t, J = 7.3
Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 181.7, 145.6, 135.4, 134.3, 132.8, 129.4, 128.6,
127.5, 127.4, 125.9, 125.5, 61.3; HRMS (ESI) m/z: [M + Na]+ Calcd for C29H20O3Na 439.1310;
Found 439.1314.
2-Hydroxy-3-(1-(p-tolyl)ethyl)naphthalene-1,4-dione (3h): orange oil (207 mg, 71% yield,
hexane/EtOAc = 8/1 as the eluent). 1H NMR (400 MHz, CDCl3) δ 8.05 (ddd, J = 27.1, 7.7, 1.1 Hz,
2H), 7.67 (dtd, J = 33.9, 7.5, 1.3 Hz, 2H), 7.53 (d, J = 2.3 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 7.09
(d, J = 8.1 Hz, 2H), 4.65 (q, J = 7.4 Hz, 1H), 2.29 (s, 3H), 1.71 (d, J = 7.0 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 184.3, 182.0, 135.8, 135.1, 133.0, 129.2, 128.9, 127.7, 127.1, 127.1, 126.0,
21.1, 17.1; HRMS (ESI) m/z: [M + Na]+ Calcd for C19H16O3Na 315.0997; Found 315.1002.
2-Hydroxy-3-(4-methoxybenzyl)naphthalene-1,4-dione (3i): orange oil (205 mg, 70% yield,
hexane/EtOAc = 7/1 as the eluent). 1H NMR (400 MHz, CDCl3) δ 8.09 (dd, J = 20.5, 7.6 Hz, 2H),
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7.74 (td, J = 7.6, 1.3 Hz, 1H), 7.67 (td, J = 7.5, 1.2 Hz, 1H), 7.41 (s, 1H), 7.32 (d, J = 8.7 Hz, 2H),
6.80 (d, J = 8.7 Hz, 2H), 3.88 (s, 2H), 3.75 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.5,
181.7, 158.1, 152.8, 135.0, 133.0, 131.0, 130.2, 129.39, 126.9, 126.1, 123.4, 113.9, 55.2, 28.2;
HRMS (ESI) m/z: [M + Na]+ Calcd for C18H14O4Na 317.0790; Found 317.0795. Physical and
spectral properties of this material were identical to those previously reported in literature.13
3-(Ferrocenylmethyl)-2-hydroxy-1,4-naphthoquinone (3j): pale green powder (186 mg, 82%
yield, hexane/EtOAc = 7/1 as the eluent). mp = 159–160 °C . 1H NMR (400 MHz, CDCl3) δ 8.10
(d, J = 7.7 Hz, 1H), 8.03 (d, J = 6.8 Hz, 1H), 7.72 (d, J = 7.6 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H),
7.36 (s, 1H), 4.26 (s, 2H), 4.16 (s, 5H), 4.03 (s, 2H), 3.65 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 184.3, 181.9, 152.5, 134.9, 132.9, 132.8, 129.4, 126.8, 126.1, 123.2, 85.7, 69.1, 68.8,
67.4, 23.2; HRMS (ESI) m/z: [M + Na]+ Calcd for C21H16FeO3Na 395.0449; Found 395.0442.
Physical and spectral properties of this material were identical to those previously reported in
literature.8b
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2-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-yl)-3-hydroxynaphthalene-1,4-dione
(3k):
orange solid (120 mg, 75% yield, hexane/EtOAc = 8/1 as the eluent). mp = 139–140 °C . 1H NMR
(400 MHz, CDCl3) δ 8.08 – 8.03 (m, 1H), 8.03 – 7.97 (m, 1H), 7.69 (td, J = 7.6, 1.2 Hz, 1H), 7.61
(td, J = 7.5, 1.1 Hz, 1H), 7.55 (s, 1H), 7.41 – 7.35 (m, 2H), 7.10 (dq, J = 5.0, 3.1, 1.9 Hz, 6H),
5.93 (s, 1H), 3.51 (m, 2H), 3.03 – 2.86 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.2, 182.1,
152.5, 141.4, 138.4, 135.2, 133.0, 132.9, 131.4, 129.9, 129.0, 127.3, 126.9, 126.3, 126.1, 125.8,
77.4, 77.1, 76.8, 48.9, 33.8; HRMS (ESI) m/z: [M + Na]+ Calcd for C25H18O3Na 389.1154; Found
389.1148.
(E)-3-(1,3-Diphenylallyl)-4-hydroxy-2H-chromen-2-one (5a): white solid (329 mg, 93% yield,
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hexane/EtOAc = 8/1 as the eluent). mp = 157–158 °C . 1H NMR (400 MHz, CDCl3) δ 7.88 – 7.82
(m, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.45 (dt, J = 9.5, 4.6 Hz, 6H), 7.41 – 7.26 (m, 7H), 6.82 (dd, J =
16.1, 6.3 Hz, 1H), 6.58 (d, J = 16.1 Hz, 1H), 5.53 (d, J = 6.0 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 163.3, 160.9, 152.8, 139.6, 136.2, 134.0, 132.2, 129.4, 128.7, 128.2, 128.1, 127.8, 126.6,
124.1, 123.2, 116.6, 115.9, 106.4, 44.1; HRMS (ESI) m/z: [M + Na]+ Calcd for C24H18O3Na
377.1154; Found 377.1162. Physical and spectral properties of this material were identical to those
previously reported in literature.6
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(E)-3-(1,3-Di-m-tolylallyl)-4-hydroxy-2H-chromen-2-one (5b): white solid (294 mg, 77% yield,
hexane/EtOAc = 8/1 as the eluent). mp = 177–179 °C . 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J =
7.7 Hz, 1H), 7.60 (t, J = 7.5 Hz, 1H), 7.41 – 7.30 (m, 4H), 7.26 (d, J = 5.0 Hz, 5H), 7.19 (d, J =
7.4 Hz, 1H), 7.13 (s, 1H), 6.94 (s, 1H), 6.75 (dd, J = 16.1, 6.2 Hz, 1H), 6.59 – 6.50 (m, 1H), 5.48
(d, J = 6.0 Hz, 1H), 2.39 (d, J = 7.3 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.2, 160.8,
152.8, 139.53, 139.3, 138.3, 136.1, 133.9, 132.2, 129.3, 128.9, 128.6, 128.6, 127.3, 125.0, 123.7,
123.1, 116.5, 106.5, 43.9, 21.6, 21.4; HRMS (ESI) m/z: [M + Na]+ Calcd for C26H22O3Na
405.1467; Found 405.1472.
(E)-3-(1,3-Di-p-tolylallyl)-4-hydroxy-2H-chromen-2-one (5c): white solid; (263 mg, 69% yield,
hexane/EtOAc = 8/1 as the eluent). mp = 104–105 °C . 1H NMR (400 MHz, CDCl3) δ 7.77 (dd, J =
7.9, 1.2 Hz, 1H), 7.58 – 7.47 (m, 1H), 7.33 – 7.25 (m, 6H), 7.19 (d, J = 7.9 Hz, 2H), 7.12 (d, J =
7.9 Hz, 2H), 6.97 (s, 1H), 6.66 (dd, J = 16.1, 6.1 Hz, 1H), 6.49 (d, J = 16.1 Hz, 1H), 5.41 (d, J =
6.0 Hz, 1H), 2.34 (d, J = 8.0 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.1, 160.8, 152.8,
138.0, 137.6, 136.4, 133.7, 133.4, 132.1, 130.1, 129.4, 128.0, 127.1, 126.5, 123.9, 123.1, 116.5,
116.0, 106.6, 43.7, 21.2, 21.1; HRMS (ESI) m/z: [M + Na]+ Calcd for C26H22O3Na 405.1467;
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Found 405.1469. Physical and spectral properties of this material were identical to those
previously reported in literature.11c
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(E)-3-(1,3-Bis(4-chlorophenyl)allyl)-4-hydroxy-2H-chromen-2-one (5d): white solid (350 mg,
83% yield, hexane/EtOAc = 8/1 as the eluent). mp = 170–172 °C . 1H NMR (400 MHz, CDCl3) δ
7.84 (d, J = 7.8 Hz, 1H), 7.61 (t, J = 7.8 Hz, 1H), 7.42 – 7.30 (m, 11H), 7.05 (s, 1H), 6.77 (dd, J =
16.1, 6.2 Hz, 1H), 6.55 – 6.43 (m, 1H), 5.45 (d, J = 5.8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)
δ 161.8, 159.8, 151.5, 136.6, 133.1, 132.8, 132.4, 131.9, 131.3, 128.3, 128.2, 127.7, 127.5, 126.6,
123.0, 122.0, 115.4, 114.5, 104.7, 42.4; HRMS (ESI) m/z: [M + Na]+ Calcd for C24H16Cl2O3Na
445.0374; Found 445.0376.
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(E)-3-(1,3-Bis(4-bromophenyl)allyl)-4-hydroxy-2H-chromen-2-one (5e): white solid (443 mg,
87% yield, hexane/EtOAc = 7/1 as the eluent). mp = 159–161 °C . 1H NMR (400 MHz, CDCl3) δ
7.79 (dd, J = 7.9, 1.2 Hz, 1H), 7.60 – 7.53 (m, 1H), 7.47 (dd, J = 22.4, 8.4 Hz, 4H), 7.35 – 7.20 (m,
7H), 6.74 (dd, J = 16.1, 6.2 Hz, 1H), 6.44 (d, J = 16.1 Hz, 1H), 5.37 (d, J = 6.0 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 163.0, 161.0, 152.7, 138.3, 134.8, 133.2, 132.5, 132.4, 131.9, 129.8,
128.8, 128.1, 124.19, 123.1, 122.2, 121.7, 116.7, 115.7, 105.8, 43.7; HRMS (ESI) m/z: [M + Na]+
Calcd for C24H16Br2O3Na 534.9343; Found 534.9346.
3-Benzhydryl-4-hydroxy-2H-chromen-2-one (5f): white solid (251 mg, 80% yield,
hexane/EtOAc = 8/1 as the eluent). mp = 176–178 °C . 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J =
7.9 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.38 (t, J = 7.2 Hz, 4H), 7.33 (dd, J = 7.6, 4.9 Hz, 3H), 7.26
(dd, J = 12.4, 7.4 Hz, 5H), 6.27 (s, 1H), 5.98 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.2,
160.7, 152.8, 140.0, 132.2, 128.8, 127.9, 124.0, 123.2, 116.5, 116.0, 107.8, 47.4; HRMS (ESI) m/z:
[M + Na]+ Calcd for C22H16O3Na 351.0997; Found 351.0989. Physical and spectral properties of
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3-(Bis(4-fluorophenyl)methyl)-4-hydroxy-2H-chromen-2-one (5g): white solid (317 mg, 87%
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yield, hexane/EtOAc = 8/1 as the eluent). mp = 175–177 °C . H NMR (400 MHz, CDCl3) δ 7.74
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(dd, J = 7.9, 1.6 Hz, 1H), 7.57 (ddd, J = 8.7, 7.3, 1.6 Hz, 1H), 7.39 – 7.34 (m, 4H), 7.33 – 7.24 (m,
3H), 7.24 – 7.15 (m, 4H), 5.91 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.4, 163.1 (d, J =
1.6 Hz), 161.0, 160.7 (d, J = 1.7 Hz), 152.7, 135.5 (d, J = 2.4 Hz), 132.4, 130.4, 130.3, 124.1,
123.2, 116.6, 116.3 (d, J = 0.6 Hz), 115.7, 107.5, 45.8; 19F NMR (376 MHz, CDCl3) δ -113.94;
HRMS (ESI) m/z: [M + Na]+ Calcd for C22H14F2O3Na 387.0809; Found 387.0814. Physical and
spectral properties of this material were identical to those previously reported in literature.14b
3-(Bis(4-chlorophenyl)methyl)-4-hydroxy-2H-chromen-2-one (5h): white solid (348 mg, 88%
1
yield, hexane/EtOAc = 8/1 as the eluent). mp = 181–182 °C . H NMR (400 MHz, CDCl3) δ 7.75
(dd, J = 8.0, 1.4 Hz, 1H), 7.62 – 7.50 (m, 1H), 7.37 – 7.01 (m, 10H), 5.92 (s, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 163.1, 160.8, 152.7, 138.1, 133.9, 132.5, 130.1, 129.7, 124.2, 123.2, 116.6,
115.7, 107.0, 46.1.; HRMS (ESI) m/z: [M + Na]+ Calcd for C22H14Cl2O3Na 419.0218; Found
419.0210. Physical and spectral properties of this material were identical to those previously
reported in literature.14b
4-Hydroxy-3-trityl-2H-chromen-2-one (5i): white solid (287 mg, 71% yield, hexane/EtOAc =
8/1 as the eluent). mp = 186–188 °C . 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 6.8 Hz, 1H), 7.53
– 7.44 (m, 7H), 7.32 – 7.26 (m, 7H), 7.21 (q, J = 7.4 Hz, 4H); 13C{1H} NMR (100 MHz, CDCl3) δ
159.9, 152.7, 143.8, 132.0, 129.6, 128.3, 126.8, 123.6, 116.3, 116.1, 110.5, 60.9; HRMS (ESI) m/z:
[M + Na]+ Calcd for C28H20O3Na 427.1310; Found 427.1316. Physical and spectral properties of
this material were identical to those previously reported in literature.14a
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4-Hydroxy-3-(1-(p-tolyl)ethyl)-2H-chromen-2-one (5j): white solid (193 mg, 69% yield,
hexane/EtOAc = 8/1 as the eluent). mp = 168–170 °C . 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J =
1.5 Hz, 1H), 7.50 (ddd, J = 8.7, 7.3, 1.6 Hz, 1H), 7.38 (d, J = 7.9 Hz, 2H), 7.30 (d, J = 8.3 Hz, 1H),
7.23 (q, J = 8.0 Hz, 3H), 4.69 (q, J = 7.2 Hz, 1H), 2.36 (s, 3H), 1.65 (d, J = 7.2 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 163.6, 159.8, 152.5, 138.3, 137.7, 131.8, 130.5, 127.2, 123.8, 122.9,
116.4, 116.2, 110.1, 34.2, 21.1, 16.6; HRMS (ESI) m/z: [M + Na]+ Calcd for C18H16O3Na
303.0997; Found 303.0991. Physical and spectral properties of this material were identical to
those previously reported in literature.14b
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4-Hydroxy-3-(4-methoxybenzyl)-2H-chromen-2-one (5k): white solid (220 mg, 78% yield,
hexane/EtOAc = 8/1 as the eluent). mp = 187–189 °C . 1H NMR (400 MHz, DMSO-d6) δ 7.79 (dd,
J = 8.2, 1.5 Hz, 1H), 7.45 – 7.39 (m, 1H), 7.21 – 7.15 (m, 2H), 6.98 (d, J = 8.7 Hz, 2H), 6.63 (d, J
= 8.7 Hz, 2H), 3.63 (s, 2H), 2.39 – 2.24 (m, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 163.3,
160.7, 158.0, 152.4, 132.3, 132.1, 129.6, 124.4, 123.8, 116.7, 116.7, 114.1, 105.2, 55.5, 28.7;
HRMS (ESI) m/z: [M + Na]+ Calcd for C17H14O4Na 305.0790; Found 305.0795. Physical and
spectral properties of this material were identical to those previously reported in literature.14b
4-Hydroxy-3-(1-(p-tolyl)but-3-en-1-yl)-2H-chromen-2-one (5l): white solid (175 mg, 57% yield,
hexane/EtOAc = 8/1 as the eluent). mp = 179–181 °C . 1H NMR (400 MHz, CDCl3) δ 7.66 (t, J =
5.7 Hz, 1H), 7.41 (ddd, J = 8.7, 7.3, 1.6 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.22 – 7.05 (m, 4H),
5.80 (ddt, J = 17.0, 10.2, 6.8 Hz, 1H), 5.09 – 4.82 (m, 2H), 4.60 (t, J = 7.7 Hz, 1H), 2.84 (qt, J =
14.3, 7.2 Hz, 2H), 2.25 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.5, 160.0, 152.6, 137.7,
137.2, 135.8, 131.8, 130.4, 127.7, 123.8, 122.8, 117.3, 116.4, 116.0, 108.6, 39.5, 35.2, 21.0; 19F
NMR (376 MHz, CDCl3) δ -117.17; HRMS (ESI) m/z: [M + Na]+ Calcd for C20H18O3Na 329.1154;
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(E)-3-(1,3-Diphenylallyl)-4-hydroxy-6-methyl-2H-chromen-2-one (5m): white solid (316 mg,
86% yield, hexane/EtOAc = 8/1 as the eluent). mp = 191–192 °C . 1H NMR (400 MHz, CDCl3) δ
7.57 (s, 1H), 7.44 – 7.18 (m, 13H), 6.76 (dd, J = 16.1, 6.3 Hz, 1H), 6.51 (d, J = 14.9 Hz, 1H), 5.47
(d, J = 6.1 Hz, 1H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.5, 161.0, 150.9, 139.9,
136.3, 133.8, 133.2, 129.3, 128.7, 128.4, 128.4, 128.1, 128.0, 127.6, 126.6, 122.8, 116.3, 115.6,
106.4, 44.0, 21.3; HRMS (ESI) m/z: [M + Na]+ Calcd for C25H20O3Na 391.1310; Found 391.1316.
Physical and spectral properties of this material were identical to those previously reported in
literature.6
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(E)-3-(1,3-Diphenylallyl)-6-fluoro-4-hydroxy-2H-chromen-2-one (5n): white solid (275 mg, 74%
1
yield, hexane/EtOAc = 8/1 as the eluent). mp = 188–190 °C . H NMR (400 MHz, CDCl3) δ 7.45
(dd, J = 8.4, 2.8 Hz, 1H), 7.42 – 7.22 (m, 12H), 6.73 (dd, J = 16.1, 6.3 Hz, 1H), 6.52 (d, J = 16.1
Hz, 1H), 5.45 (d, J = 5.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.8, 160.0 (d, J = 3.1
Hz), 157.4, 148.8 (d, J = 1.6 Hz), 139.2, 136.0, 134.2, 129.4, 128.7, 128.2, 128.0, 127.9, 127.7,
126.6, 119.6 (d, J = 24.8 Hz), 118.1 (d, J = 8.3 Hz), 116.8 (d, J = 9.1 Hz), 108.9 (d, J = 25.4 Hz),
107.2, 44.1; HRMS (ESI) m/z: [M + Na]+ Calcd for C24H17FO3Na 395.1059; Found 395.1067.
(E)-6-Bromo-3-(1,3-diphenylallyl)-4-hydroxy-2H-chromen-2-one (5o): white solid (337 mg, 78%
1
yield, hexane/EtOAc = 8/1 as the eluent). mp = 187–189 °C . H NMR (400 MHz, CDCl3) δ 7.91
(d, J = 2.3 Hz, 1H), 7.62 (dd, J = 8.8, 2.4 Hz, 1H), 7.43 – 7.15 (m, 13H), 6.73 (dd, J = 16.1, 6.3 Hz,
1H), 6.52 (dd, J = 16.1, 1.4 Hz, 1H), 5.44 (dd, J = 6.3, 1.7 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 162.6, 159.7, 151.5, 139.2, 136.0, 135.0, 134.2, 129.5, 128.7, 128.2, 128.1, 127.9, 127.7,
126.6, 125.9, 118.3, 117.5, 116.8, 107.3, 44.1; HRMS (ESI) m/z: [M + Na]+ Calcd for
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C24H17BrO3Na 455.0259; Found 455.0253.
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(E)-3-(1,3-Diphenylallyl)-4-hydroxyquinolin-2(1H)-one (5p): white solid (141 mg, 40% yield,
8
9
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hexane/EtOAc = 7/1 as the eluent). mp = 189–191 °C . H NMR (400 MHz, CDCl3) δ 11.90 (s,
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1H), 7.84 (d, J = 8.1 Hz, 1H), 7.48 – 7.11 (m, 15H), 6.86 – 6.79 (m, 1H), 6.53 (d, J = 16.1 Hz, 1H),
5.79 (d, J = 5.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 164.8, 159.3, 140.6, 137.6, 136.5,
133.3, 130.9, 129.2, 129.2, 128.6, 128.3, 127.9, 127.3, 126.6, 122.8, 122.1, 115.8, 115.5, 111.7,
43.0; HRMS (ESI) m/z: [M + Na]+ Calcd for C24H19NO2Na 376.1313; Found 376.1317.
(E)-4-Amino-3-(1,3-diphenylallyl)-2H-chromen-2-one (5q): white solid (318 mg, 90% yield,
hexane/EtOAc = 5/1 as the eluent). mp = 156–158 °C . 1H NMR (400 MHz, CDCl3) δ 7.53 – 7.46
(m, 1H), 7.46 – 7.34 (m, 5H), 7.33 – 7.17 (m, 8H), 6.73 (dd, J = 15.9, 7.0 Hz, 1H), 6.56 (d, J =
16.0 Hz, 1H), 5.57 (d, J = 6.9 Hz, 1H), 5.06 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.3,
152.8, 149.7, 140.8, 137.0, 132.6, 131.7, 128.9, 128.6, 127.7, 127.6, 127.2, 127.0, 126.4, 123.6,
120.8, 117.5, 114.8, 100.4, 44.1; HRMS (ESI) m/z: [M + Na]+ Calcd for C24H19NO2Na 376.1313;
Found 376.1315.
4-Hydroxy-3-(1-phenylpropyl)-2H-chromen-2-one (5r): white solid (757 mg, 54% yield,
hexane/EtOAc = 8/1 as the eluent). mp = 179–182 °C; 1H NMR (400 MHz, CDCl3) δ 7.63 (dd, J =
8.0, 1.3 Hz, 1H), 7.48 – 7.37 (m, 3H), 7.33 (t, J = 7.6 Hz, 2H), 7.27 – 7.12 (m, 3H), 6.45 (s, 1H),
4.46 (t, J = 7.7 Hz, 1H), 2.26 – 1.94 (m, 2H), 0.99 (t, J = 7.3 Hz, 3H).; 13C{1H} NMR (100 MHz,
CDCl3) δ 163.8, 160.0, 152.6, 141.2, 131.8, 129.6, 127.7, 127.6, 123.8, 122.8, 116.4, 116.0, 108.9,
41.7, 24.0, 12.4.; HRMS (ESI) m/z: [M + Na]+ Calcd for C18H16O3Na 303.0997; Found 303.1002.
Physical and spectral properties of this material were identical to those previously reported in
literature.15
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4-Hydroxy-3-(1,2,3,4-tetrahydronaphthalen-1-yl)-2H-chromen-2-one (5s): white solid (950
mg, 65% yield, hexane/EtOAc = 8/1 as the eluent). mp = 173–175°C; 1H NMR (400 MHz, CDCl3)
δ 7.67 (dd, J = 7.9, 1.3 Hz, 1H), 7.52 (ddd, J = 8.8, 7.4, 1.6 Hz, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.26
(s, 1H), 7.25 (s, 2H), 7.24 – 7.17 (m, 2H), 5.86 (s, 1H), 4.62 (t, J = 6.9 Hz, 1H), 2.92 (t, J = 5.0 Hz,
2H), 2.28 – 2.18 (m, 1H), 1.99 – 1.82 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.7, 159.9,
152.5, 138.1, 134.6, 131.8, 130.6, 129.6, 128.0 127.5, 123.9, 123.0 116.4, 116.2, 109.4, 36.4, 29.8,
29.3, 21.7; HRMS (ESI) m/z: [M + Na]+ Calcd for C19H16O3Na 315.0997; Found 315.0992.
Physical and spectral properties of this material were identical to those previously reported in
literature.14b
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(E)-3-(1-(Benzo[d][1,3]dioxol-5-yl)-4,4-dimethylpent-2-en-1-yl)-4-hydroxy-2H-chromen-2-on
1
e (5t): white solid (1.47 g, 78% yield, hexane/EtOAc = 8/1 as the eluent). mp = 156–157 °C; H
NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 7.9, 1.4 Hz, 1H), 7.57 – 7.51 (m, 1H), 7.34 – 7.26 (m,
3H), 6.78 (s, 3H), 5.96 (s, 2H), 5.91 (dd, J = 16.0, 5.5 Hz, 1H), 5.65 (dd, J = 16.0, 1.8 Hz, 1H),
5.13 (dd, J = 5.4, 1.6 Hz, 1H), 1.05 (s, 9H).; 13C{1H} NMR (100 MHz, CDCl3) δ 163.0, 161.0,
152.7, 148.4, 147.0, 146.8, 133.5, 132.1, 124.4, 123.9, 123.1, 120.9, 116.5, 116.0, 108.8, 108.6,
106.4, 101.2, 43.5, 33.4, 29.4.; HRMS (ESI) m/z: [M + Na]+ Calcd for C23H22O5Na 401.1365;
Found 401.1363.
General Procedure for Preparation of 6 and 7
A mixture of the substrate 1a or 4a (1.2 mmol), substrate 2 (1.0 mmol), in HFIP (5.0 mL) was
stirred at room temperature for 10 min. Extra DDQ (1.0 equiv) was added to the reaction mixture
after the alkylation reaction of 1a or 4a with 2 was completed. The mixture was continued to be
stirred for 1h at room temperature. Upon completion of the reaction, the resulted mixture was
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concentrated in vacuo. The residue was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) to give the pure product 6 and 7.
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2,4-Diphenyl-2H-benzo[g]chromene-5,10-dione (6a): orange oil (284 mg, 78% yield,
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hexane/EtOAc = 7/1 as the eluent). H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 8.6 Hz, 1H), 8.07
(d, J = 7.6 Hz, 1H), 7.75 (t, J = 8.3 Hz, 1H), 7.71 – 7.64 (m, 1H), 7.58 (s, 1H), 7.42 (d, J = 7.6 Hz,
4H), 7.30 (t, J = 7.6 Hz, 4H), 7.21 (t, J = 6.7 Hz, 2H), 7.01 (dd, J = 15.8, 9.0 Hz, 1H), 6.62 (d, J =
15.8 Hz, 1H), 5.39 (d, J = 9.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 181.3, 179.4, 154.8,
138.6, 137.5, 135.2, 134.3, 133.2, 132.2, 131.1, 129.4, 128.9, 128.1, 127.8, 127.7, 127.4, 126.7,
126.1, 124.2, 121.0, 78.1; HRMS (ESI) m/z: [M + Na]+ Calcd for C25H16O3Na 387.0997; Found
387.1000. Physical and spectral properties of this material were identical to those previously
reported in literature.6
2,4-Bis(4-chlorophenyl)-2H-benzo[g]chromene-5,10-dione (6b): orange oil (307 mg, 71% yield,
1
hexane/EtOAc = 7/1 as the eluent). H NMR (400 MHz, CDCl3) δ 8.12 – 8.05 (m, 1H), 8.01 –
7.95 (m, 1H), 7.76 – 7.65 (m, 2H), 7.48 (d, J = 8.5 Hz, 2H), 7.36 (dd, J = 11.0, 8.5 Hz, 4H), 7.19
(d, J = 8.4 Hz, 2H), 6.11 (d, J = 4.6 Hz, 1H), 5.91 (d, J = 4.6 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 181.2, 179.2, 136.8, 135.8, 135.5, 134.5, 133.9, 133.5, 132.0, 130.9, 129.2, 129.0, 128.7,
128.4, 126.7, 126.2, 123.8, 120.6; HRMS (ESI) m/z: [M + Na]+ Calcd for C25H14Cl2O3Na
455.0218; Found 455.0221.
2,4-Diphenyl-2H,5H-pyrano[3,2-c]chromen-5-one (7a): white solid (282 mg, 80% yield,
hexane/EtOAc = 7/1 as the eluent). mp = 158–160 °C . 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J =
7.2 Hz, 1H), 7.60 (t, J = 6.2 Hz, 3H), 7.46 (d, J = 7.4 Hz, 3H), 7.42 – 7.39 (m, 5H), 7.33 (d, J =
4.7 Hz, 1H), 7.30 (s, 2H), 6.19 (d, J = 4.1 Hz, 1H), 5.81 (d, J = 4.1 Hz, 1H); 13C{1H} NMR (100
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MHz, CDCl3) δ 161.4, 153.6, 137.9, 135.3, 132.6, 129.3, 128.9, 128.0, 127.5, 127.5, 124.0, 123.3,
120.3, 1167, 115.3, 102.9; HRMS (ESI) m/z: [M + Na]+ Calcd for C24H16O3Na 375.0997; Found
375.1001. Physical and spectral properties of this material were identical to those previously
reported in literature.6
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2,4-Di-m-tolyl-2H,5H-pyrano[3,2-c]chromen-5-one (7b): white solid (186 mg, 49% yield,
hexane/EtOAc = 7/1 as the eluent). mp = 157-159 °C . 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J =
7.9, 1.5 Hz, 1H), 7.53 (ddd, J = 8.7, 7.3, 1.6 Hz, 1H), 7.35 (d, J = 2.6 Hz, 2H), 7.30 (dt, J = 8.0,
3.9 Hz, 2H), 7.26 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.18 – 7.11 (m, 4H), 6.08 (d, J = 4.1 Hz, 1H),
5.73 (d, J = 4.1 Hz, 1H), 2.37 (d, J = 4.3 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.4,
158.7, 153.6, 138.7, 138.3, 137.9, 137.5, 135.2, 132.5, 130.0, 128.8, 128.7, 128.2, 128.1, 127.8,
124.7, 124.5, 123.9, 123.3, 120.3, 116.6, 115.3, 102.9, 79.0, 21.5, 21.5; HRMS (ESI) m/z: [M +
Na]+ Calcd for C26H20O3Na 403.1310; Found 403.1316.
2,4-Di-p-tolyl-2H,5H-pyrano[3,2-c]chromen-5-one (7c): light yellow oil (213 mg, 56% yield,
hexane/EtOAc = 7/1 as the eluent). 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 9.1 Hz, 1H), 7.52 (t,
J = 7.8 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.3 Hz, 1H), 7.22 (t, Hz, 5H), 7.17 (d, J =
8.0 Hz, 2H), 6.09 (d, J = 4.2 Hz, 1H), 5.73 (d, J = 4.3 Hz, 1H), 2.37 (d, J = 5.6 Hz, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 161.3, 153.6, 139.3, 137.6, 135.2, 135.0, 132.5, 129.6, 128.7, 127.7,
127.3, 123.9, 123.3, 119.8, 116.6, 115.4, 102.9, 21.3, 21.3; HRMS (ESI) m/z: [M + Na]+ Calcd for
C26H20O3Na 403.1310; Found 403.1313.
2,4-Bis(4-bromophenyl)-2H,5H-pyrano[3,2-c]chromen-5-one (7d): light yellow oil (376 mg, 74%
yield, hexane/EtOAc = 7/1 as the eluent). 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.9 Hz, 1H),
7.55 (d, J = 8.3 Hz, 3H), 7.48 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.35 – 7.27 (m, 2H),
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7.19 (d, J = 8.4 Hz, 2H), 6.09 (d, J = 4.3 Hz, 1H), 5.71 (d, J = 4.3 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 161.4, 153.6, 136.9, 136.6, 134.7, 133.0, 132.2, 131.1, 129.2, 129.1, 124.2, 123.6,
123.3, 122.1, 116.8, 114.9, 102.4; HRMS (ESI) m/z: [M + Na]+ Calcd for C24H14Br2O3Na
532.9187; Found 532.9193.
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
NMR (1H, 13C) spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: lijinshan@tzc.edu.cn
ORCID
Jinshan Li: 0000-0001-8033-5932
Notes
The authors declare no competing financial interest.
ACKNOWLEDGEMENTS
This work was supported by Natural Science foundation of Zhejiang Province (No.
LQ20B020005).
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